Detachment-induced autophagy during anoikis and lumen formation in epithelial acini

Autophagy
Jayanta Debnath

Abstract

The individual units (called acini) comprising glandular epithelium possess a hollow lumen that is filled in early epithelial cancers. While investigating the generation of this hollow lumen using an in vitro three-dimensional (3D) epithelial cell culture model, we observed extensive autophagy in dying cells during lumen formation, and thus, proposed that excessive self-eating may promote cell death in the lumen. However, we now reassess this hypothesis. Because cells in the lumen die due to extracellular matrix (ECM) deprivation (anoikis), we tested if autophagy is regulated by ECM detachment. We discovered that detachment strongly induces autophagy in epithelial cells, even when apoptosis is inhibited by Bcl-2 expression. RNAi-mediated depletion of autophagy-related (ATG) genes inhibits detachment-induced autophagy, resulting in increased apoptosis and reduced clonogenic recovery following anoikis. Similarly, during 3D morphogenesis, ATG-depletion enhances luminal apoptosis and fails to elicit long-term luminal survival and filling, even when combined with apoptotic inhibition. Thus, autophagy promotes epithelial cell survival during anoikis. These results broach the possibility that autophagy contributes to the survival of t...Continue Reading

Citations

Jan 15, 2014·Oncogene·A Avivar-ValderasJ A Aguirre-Ghiso
Jul 27, 2011·Neuro-oncology·Stephanie L LomonacoChaya Brodie
Nov 7, 2012·Neuroscience Letters·Younghye MoonWoong Sun
Jun 10, 2015·Autophagy·Victor H VillarRaúl V Durán
Aug 27, 2011·European Journal of Cell Biology·Agnieszka SobolewskaMalgorzata Gajewska
Feb 16, 2012·Journal of Cellular and Molecular Medicine·Minshu YuElise C Kohn
Aug 22, 2013·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Jie YangZhenyi Ma
Mar 24, 2016·Apoptosis : an International Journal on Programmed Cell Death·Dahong YaoJinhui Wang
May 1, 2015·Cell Cycle·Kewei Wang
Mar 10, 2015·Molecular Cancer·Zhenyi SuQiang Yu
Apr 17, 2010·The American Journal of Pathology·Núria EritjaXavi Dolcet
Nov 16, 2017·Genes & Development·Hui-Wen LueGeorge V Thomas
Jun 5, 2018·Autophagy·Christopher M DowerHong-Gang Wang
Apr 17, 2015·Journal of Virology·Julie A Fotheringham, Nancy Raab-Traub
Jun 29, 2011·Molecular and Cellular Biology·Alvaro Avivar-ValderasJulio A Aguirre-Ghiso
Nov 30, 2018·International Journal of Molecular Sciences·Cristina Trejo-SolísJulio Sotelo
Jul 28, 2020·Pharmaceuticals·Angel Escamilla-RamírezCristina Trejo-Solís
Sep 30, 2015·Oncotarget·Joe R DelaneyDwayne G Stupack
Sep 19, 2020·Experimental & Molecular Medicine·Hee Chan YooJung Min Han
Jun 28, 2016·Oncology Letters·Y I LiDouglas R Hurst
Dec 10, 2016·Journal of Molecular Biology·Ariadne Vlahakis, Jayanta Debnath
Nov 14, 2020·International Journal of Molecular Sciences·Clara PerroneRossella Rota
Aug 21, 2019·Seminars in Cancer Biology·Chandan Kanta DasMahitosh Mandal

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Parkinson's Disease & Autophagy (MDS)

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Autophagy & Aging: Inhibitors

The feed focuses on the role of nuclear export inhibitors and their effect on autophagy and the aging process.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.